<it>In silico </it>identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach
<p>Abstract</p> <p>Background</p> <p>The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory net...
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Format: | Article |
Language: | English |
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BMC
2009-07-01
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Series: | BMC Genomics |
Online Access: | http://www.biomedcentral.com/1471-2164/10/314 |
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author | Adjaye James Lehrach Hans Vingron Martin Bais Abha S Chavez Lukas Herwig Ralf |
author_facet | Adjaye James Lehrach Hans Vingron Martin Bais Abha S Chavez Lukas Herwig Ralf |
author_sort | Adjaye James |
collection | DOAJ |
description | <p>Abstract</p> <p>Background</p> <p>The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory network governed by the transcription factors OCT4, SOX2 and NANOG. Recent studies on reprogramming somatic cells to induced pluripotent stem cells highlight OCT4 as a key regulator of pluripotency.</p> <p>Results</p> <p>We have carried out an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments along with promoter sequence analysis of putative target genes) and identified a core OCT4 regulatory network in human embryonic stem cells consisting of 33 target genes. Enrichment analysis with these target genes revealed that this integrative analysis increases the functional information content by factors of 1.3 – 4.7 compared to the individual studies. In order to identify potential regulatory co-factors of OCT4, we performed a <it>de novo </it>motif analysis. In addition to known validated OCT4 motifs we obtained binding sites similar to motifs recognized by further regulators of pluripotency and development; e.g. the heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC transcriptional activity that leads to cell growth and proliferation.</p> <p>Conclusion</p> <p>Our analysis shows how heterogeneous functional information can be integrated in order to reconstruct gene regulatory networks. As a test case we identified a core OCT4-regulated network that is important for the analysis of stem cell characteristics and cellular differentiation. Functional information is largely enriched using different experimental results. The <it>de novo </it>motif discovery identified well-known regulators closely connected to the OCT4 network as well as potential new regulators of pluripotency and differentiation. These results provide the basis for further targeted functional studies.</p> |
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id | doaj.art-95378d011fe4437b95e49584bdccf323 |
institution | Directory Open Access Journal |
issn | 1471-2164 |
language | English |
last_indexed | 2024-04-13T00:09:18Z |
publishDate | 2009-07-01 |
publisher | BMC |
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series | BMC Genomics |
spelling | doaj.art-95378d011fe4437b95e49584bdccf3232022-12-22T03:11:08ZengBMCBMC Genomics1471-21642009-07-0110131410.1186/1471-2164-10-314<it>In silico </it>identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approachAdjaye JamesLehrach HansVingron MartinBais Abha SChavez LukasHerwig Ralf<p>Abstract</p> <p>Background</p> <p>The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory network governed by the transcription factors OCT4, SOX2 and NANOG. Recent studies on reprogramming somatic cells to induced pluripotent stem cells highlight OCT4 as a key regulator of pluripotency.</p> <p>Results</p> <p>We have carried out an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments along with promoter sequence analysis of putative target genes) and identified a core OCT4 regulatory network in human embryonic stem cells consisting of 33 target genes. Enrichment analysis with these target genes revealed that this integrative analysis increases the functional information content by factors of 1.3 – 4.7 compared to the individual studies. In order to identify potential regulatory co-factors of OCT4, we performed a <it>de novo </it>motif analysis. In addition to known validated OCT4 motifs we obtained binding sites similar to motifs recognized by further regulators of pluripotency and development; e.g. the heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC transcriptional activity that leads to cell growth and proliferation.</p> <p>Conclusion</p> <p>Our analysis shows how heterogeneous functional information can be integrated in order to reconstruct gene regulatory networks. As a test case we identified a core OCT4-regulated network that is important for the analysis of stem cell characteristics and cellular differentiation. Functional information is largely enriched using different experimental results. The <it>de novo </it>motif discovery identified well-known regulators closely connected to the OCT4 network as well as potential new regulators of pluripotency and differentiation. These results provide the basis for further targeted functional studies.</p>http://www.biomedcentral.com/1471-2164/10/314 |
spellingShingle | Adjaye James Lehrach Hans Vingron Martin Bais Abha S Chavez Lukas Herwig Ralf <it>In silico </it>identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach BMC Genomics |
title | <it>In silico </it>identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach |
title_full | <it>In silico </it>identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach |
title_fullStr | <it>In silico </it>identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach |
title_full_unstemmed | <it>In silico </it>identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach |
title_short | <it>In silico </it>identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach |
title_sort | it in silico it identification of a core regulatory network of oct4 in human embryonic stem cells using an integrated approach |
url | http://www.biomedcentral.com/1471-2164/10/314 |
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